Comparison of Body Distribution of Poly(vinyl alcohol) with Other Water-soluble Polymers after Intravenous Administration

Abstract

The body distribution of poly(vinyl alcohol) (PVA) with molecular weights (MW) from 14,800 to 434,000 Da was investigated after intravenous administration and compared with that of other water-soluble polymers such as poly(ethylene glycol) (PEG), gelatin, dextran, and pullulan. The half-life of PVA in the circulation was prolonged from 90 min (MW 14,800 Da) to 23 h (MW 434,000 Da), similar to that of PEG which had a half-life of 30 min (MW 6000) and 20 h (MW 170,000). However, the half-life of PVA was much longer than that of other polymers when compared at a similar molecular weight. PVA was located in most organs but with very small accumulation. An insignificant interaction of PVA with cell components, such as macrophages and blood cells, was observed. Similar to PEG, the excretion rate of PVA at the glomeruli was rapidly reduced around 30,000 Da, as the molecular weight increased. These results indicate that the half-life of intravenously injected PVA in the blood was mainly determined by the permeation characteristics of the kidney.

Synthesis of Poly(vinyl alcohol)-Doxorubicin Conjugates Containing cis-Aconityl Acid-Cleavable Bond and Its Isomer Dependent Doxorubicin Release

“…Its structure was confirmed by one-and two-dimensional NMR ( 1 H, 13 Preparation of PVA-ADOX Conjugates Ethylenediamine residues were introduced to the hydroxyl groups of PVA molecules by the 1,1Ј-carbonyldiimidazole (CDI) activation method. [18][19][20] Four milliliters of dimethyl sulfoxide (DMSO) containing CDI (74 mg) was added to 400 mg of PVA dissolved in 60 ml of DMSO, followed by stirring for 1 h at room temperature. After several precipitations in butanol to remove unreacted reagents, the fraction of CDI-activated PVA was dried in vacuo.…”

“…The excitation and emission wavelength were set at 470 nm and 560 nm, respectively. A 4.6ϫ150 mm, 5-mm particle size, C 18 reversedphase column (Cosmosil 5C 18 , Nacalai, Kyoto, Japan) was used at ambient temperature. The mobile phase was 34% acetonitrile in 1% triethylamine adjusted to pH 4.0 with formic acid.…”

“…Analysis of ADOX was carried out using a Shimadzu liquid chromatographic system (LC-6A, Kyoto, Japan) with a variable-wavelength UV detector (SPD-6A) operated at 200 nm. A 4.6ϫ150 mm, 5-mm particle size, C 18 reversed-phase column (Cosmosil 5C 18 , Nacalai, Kyoto, Japan) was used at ambient temperature. The mobile phase was (NH 4 ) 2 CO 3 (3 w/w%) : methanol : acetonitrileϭ50 : 45 : 5, v/v/v.…”

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

“…Similarly, PVA elimination rates depend largely on the injection site and the molecular weight of the polymer, with the cut off size for glomerular filtration being 30 kDa. 49 Studies examining the fate of larger molecular weights of PVA have shown accumulation within the liver and spleen of rats. 50 From these collective studies it is clear that the molecular weight of the polymer should be as low as possible to ensure complete elimination.…”

Characteristics of Tissue Distribution of Various Polysaccharides as Drug Carriers: Influences of Molecular Weight and Anionic Charge on Tumor Targeting

“…6) Recently, the N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-DXR conjugate, called PK1, has entered clinical development in the UK 7,8) and its Phase 1 results 9) showed that by conjugating the drug with a macromolecule, its distribution properties could be altered depending on the properties of the carrier macromolecules. 10,11) Various macromolecules, such as immunoglobulins, 12) albumin, 13) polyaminoacids, [14][15][16][17][18][19] synthetic polymers, 20,21) and polysaccharides, [22][23][24][25] have traditionally been used as drug carriers; however, this approach does not always produce the desired results in vivo since the distribution characteristics of these drug carriers has so far not been characterized and, therefore, is not well known. In particular, there is not enough information about the distribution properties and physicochemical characteristics of polysaccharides to select suitable drug carriers for tumor targeting.…”